The overall goal of this clinical project is to test the value of accelerated fractionation in the post-op radiotherapy of head and neck cancer. In the treatment of SCC of the head and neck, both definitively and postoperatively, protraction of overall, treatment time and/or split-course treatment has been shown to have an adverse effect on tumor control unless the total dose is increased to compensate for treatment protraction. In a randomized study performed during the current granting period to determine the optimum dose of conventionally fractionated radiotherapy for post-op treatment of head and neck cancers, we found no dose-response for tumor control in lover risk patients between 57.6 Gy and 63.0 Gy, or in higher risk patients between 63.0 Gy and 68.4 Gy. Patients receiving 68.4 Gy did, however sustain a higher incidence of late treatment-related complications. We hypothesize that the additional time required to deliver the higher doses at 1.8 Gy/day in this trial may have reduced the net effective dose increments to levels too small to be resolvable in terms of tumor control, whereas the probability of late complications would not have been influenced by overall treatment time. A new randomized study is, therefore, planned in which patients with a moderate to high risk of recurrence will be randomly assigned to treatment with standard fractionation (63 Gy/35 fx/7 wks) versus accelerated fractionation using the concomitant boost technique (63 Gy/35 fx/5 wks). Because increased acute toxicity is associated with accelerated fractionation, predictive identification of patients who will benefit from this approach is desirable. We, therefore, plan to incorporate into the clinical trial, assays of the pretreatment proliferation kinetics and inherent radiosensitivity of the tumors. The hypothesis we will test is that tumors with the shortest potential doubling times will be those most likely to show improved control rates with accelerated fractionation. In analyzing the data, the confounding influence of inherent cellular radiosensitivity on the predictive value of potential doubling time will be considered. The study will answer two questions: 1) Whether accelerated fractionation confers an across-the-board benefit compared with conventional fractionation in the postoperative radiotherapy setting, and 2) Whether radiobiological measurements done on the surgical specimen can predictively identify with patients who will benefit from accelerated fractionation.